Veratrum nigrum inhibits the estrogenic activity of salvia miltiorrhiza bunge in vivo and in vitro.

BACKGROUND: As recorded in the 18 incompatible medicaments of Traditional Chinese Medicine theory, the combined use of Salvia miltiorrhiza bunge (SM) and Veratrum nigrum (VN) could induce toxicity and has been prohibited for thousands of years in China. However, the theory has been validated due to lack of evidence. Previous studies have focused on the chemical constituents that are responsible for the toxicity of the two agents. PURPOSE: This study offers preliminary insight into the pharmacodynamics and mechanism of estrogenic activity responsible for their incompatibility. STUDY DESIGN: We undertook a characterization of the interaction between estrogenic activities of SM and VN using in vivo models of immature and ovariectomized (OVX) mice, and in vitro studies focused on the estrogen receptor (ER) pathway for further mechanism. METHODS: Immature and OVX mice were treated intragastrically with SM at doses of 1.6, 3.2 g/kg, or combine with 0.045 g/kg VN and 0.005 g/kg the ER antagonist ICI182, 780 for elucidating the effects on estrogenic activity in reproductive tissues, E2 secretion, and the ER mechanism. ERα/ß binding experiments and ERα/ß transcriptional activity were performed in order to evaluate the biological action exerted through ERs. RESULTS: VN decreased the estrogenic efficacy of SM in promoting the development of the uterus and vagina in immature mice, and reversing the atrophy of reproductive tissues in OVX mice. VN interfered with the estrogenic efficacy of SM by decreasing the serum estradiol and the upregulation of ERα and ERß expressions in reproductive tissues by treatment with SM. VN antagonized the estrogenic efficacy of SM in promoting the viability of MCF-7 cells and stimulating the binding ability with ERα and ERß, and increasing ERα/ß-estrogen response element (ERE) luciferase activity. CONCLUSIONS: This study provided evidence that the combined use of SM and VN could induce unfavorable effects. VN decreased the estrogenic activity of SM, which might be related to the regulation of estrogen secretion and ERs through the ER-ERE pathway.

Salvia miltiorrhiza bunge increases estrogen level without side effects on reproductive tissues in immature/ovariectomized mice.

Salvia miltiorrhiza bunge(SM) is a popular herb for alleviating menopausal symptoms, although the scientific evidence of applying SM to estrogen replacement therapy is limited. In this study, we characterized the estrogenic activity of SM using in vivo models of immature and ovariectomized (OVX) mice and performed in vitro studies focusing on the estrogen receptor (ER) pathway for further molecular characterizations. SM treatments demonstrated significant estrogenic activity by promoting the development of uterus and vagina in immature mice, restoring the estrus cycle and reversing the atrophy of reproductive tissues in OVX mice, as well as increasing the expressions of ERα and ERß at protein and mRNA level in the reproductive tissues. Meanwhile, SM significantly increased estradiol in serum, and decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the circulation of immature and OVX mice. SM could stimulate the binding effect of ERα and ERß, and significantly induce ERα/ß-estrogen response element (ERE) luciferase reporter gene expression. All these activities were inhibited by the ER antagonist ICI182, 780. This study demonstrates SM exerts estrogenic effects by stimulating biosynthesis of estrogen and increasing ERs in target tissues without side effects on reproductive tissues and through ER-ERE-dependent pathway.

Effect of the Interaction of Veratrum Nigrum with Panax Ginseng on Estrogenic Activity In Vivo and In Vitro.

Panax ginseng (GS) and Veratrum nigrum (VN) are representative of incompatible pairs in "eighteen antagonistic medicaments" that have been recorded in the Chinese medicinal literature for over 2,000 years. However, evidence linking interference effects with combination use is scare. Based on the estrogen-like effect of GS described in our previous studies, we undertake a characterization of the interaction on estrogenic activity of GS and VN using in vivo models of immature and ovariectomized (OVX) mice and in vitro studies with MCF-7 cells for further mechanism. VN decreased the estrogenic efficacy of GS on promoting the development of the uterus and vagina in immature mice, and reversing the atrophy of reproductive tissues in OVX mice. VN interfered with the estrogenic efficacy of GS by decreasing the increase of the serum estradiol and the up-regulation of ERα and ERß expressions by treatment with GS. And VN antagonized the estrogenic efficacy of GS on promoting the viability of MCF-7 cells and up-regulation of protein and gene expressions of ERs. In conclusion, this study provided evidence that GS and VN decreased effects on estrogenic activity, which might be related to regulation of estrogen secretion and ERs.

Short-time QiBaoMeiRan Formula Treatment Exerts Estrogenic Activities without Side Effects on Reproductive Tissues in Immature Mice.

The Chinese herbal preparation QiBaoMeiRan formula (QBMR) displayed estrogenic effects in ovariectomized rats after long-term administration in a previous study. The uterus and vagina are negatively influenced by estrogens in hormone therapy. While QBMR is known to be a phytoestrogen, its estrogenic effects and safety on reproductive tissues after short-term administration and its mechanism via estrogen receptor (ER) pathway haven't been studied. Here, we characterized its estrogenic effects using immature mice together with in vitro studies for further molecular characterization. Immature mice were treated with QBMR at doses of 1.125, 2.25, and 4.5 g/kg for 7 days. 1.125 and 2.25 g/kg QBMR promoted the growth and development of uterus and vagina, and upregulated ERα and ERß expression in reproductive tissues. QBMR had a stimulatory effect on proliferating cell nuclear antigen in vagina but not in uterus, and was without any influence on ki-67 antigen in uterus and vagina. QBMR significantly induced luciferase expression from the ERα/ß-estrogen response element (ERE) luciferase reporter and upregulated ERα and ERß expressions in MCF-7 cells, which were significantly inhibited by estrogen antagonist ICI182,780. This study demonstrated QBMR exerts estrogenic effects on reproductive tissues without side effects and through ER-ERE-dependent pathway.